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Aim <p>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and oxidative stress (OS). This study investigated whether <i>pre-miRNA-499a</i> (rs3746444) and <i>pre-miRNA-146a</i> (rs2910164) polymorphisms are associated with RA susceptibility and disease severity, and evaluated OS/antioxidant and inflammatory profiles in relation to disease activity score 28 based on erythrocyte sedimentation rate (DAS28‑ESR) and anti–cyclic citrullinated peptide (anti-CCP)in an Erbil-based cohort.</p> Patients and methods <p>Fifty RA patients and fifty healthy controls were genotyped by amplification refractory mutation system (ARMS-PCR). Serum OS and antioxidant markers, inflammatory cytokines, and trace elements were assessed, and their relationships with DAS28‑ESR and anti-CCP were analyzed.</p> Results <p>The rs3746444 TC genotype was significantly associated with increased RA risk (odds ratio (OR) = 2.708, <i>p</i> = 0.0209) and with higher DAS28‑ESR and anti-CCP levels (<i>p</i> = 0.020), whereas rs2910164 showed no significant association. RA patients demonstrated a disturbed redox balance and inflammatory activation compared with controls. Among the measured variables, interferon (IFN)-γ was the strongest predictor of both disease activity and anti-CCP titers (<i>p</i> &lt; 0.001), with interleukin (IL)-10 and superoxide dismutase (SOD) showing an inverse relationship.</p> Conclusion <p>pre-miRNA-499a rs3746444, particularly the TC genotype, is linked to RA susceptibility and greater disease severity in this population. IFN-γ, together with key antioxidant/inflammatory indicators, may support monitoring of RA activity and stratification of patients for more tailored management.</p> Graphical Abstract <p></p>

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Genetic variants of pre-miRNA-499a and oxidative-immune biomarkers predict disease severity in rheumatoid arthritis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月10日

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  • Kovan Faidhalla Jalal,
  • Niaz Albarzinji,
  • Shukur Wasman Smail,
  • Mustafa Fahmi Rajab,
  • Ashraf Kakoo,
  • Mudhir Sabir Shekha

摘要

Aim

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and oxidative stress (OS). This study investigated whether pre-miRNA-499a (rs3746444) and pre-miRNA-146a (rs2910164) polymorphisms are associated with RA susceptibility and disease severity, and evaluated OS/antioxidant and inflammatory profiles in relation to disease activity score 28 based on erythrocyte sedimentation rate (DAS28‑ESR) and anti–cyclic citrullinated peptide (anti-CCP)in an Erbil-based cohort.

Patients and methods

Fifty RA patients and fifty healthy controls were genotyped by amplification refractory mutation system (ARMS-PCR). Serum OS and antioxidant markers, inflammatory cytokines, and trace elements were assessed, and their relationships with DAS28‑ESR and anti-CCP were analyzed.

Results

The rs3746444 TC genotype was significantly associated with increased RA risk (odds ratio (OR) = 2.708, p = 0.0209) and with higher DAS28‑ESR and anti-CCP levels (p = 0.020), whereas rs2910164 showed no significant association. RA patients demonstrated a disturbed redox balance and inflammatory activation compared with controls. Among the measured variables, interferon (IFN)-γ was the strongest predictor of both disease activity and anti-CCP titers (p < 0.001), with interleukin (IL)-10 and superoxide dismutase (SOD) showing an inverse relationship.

Conclusion

pre-miRNA-499a rs3746444, particularly the TC genotype, is linked to RA susceptibility and greater disease severity in this population. IFN-γ, together with key antioxidant/inflammatory indicators, may support monitoring of RA activity and stratification of patients for more tailored management.

Graphical Abstract